1. Field of the Invention
The present invention provides and includes monoclonal antibodies (MoAbs or mAbs) specific or preferentially selective for PCBP-1 antigens, hybridoma lines that secrete these PCBP-1 antibodies or antibody fragments, and the use of such antibodies and antibody fragments to detect PCBP-1 antigens, particularly those expressed by cancer cells. The present invention also includes antibodies that are specific for or show preferential binding to a soluble form of PCBP-1. The present invention further includes chimeric and humanized antibodies, processes for producing monoclonal, chimeric, and humanized antibodies using recombinant DNA technology, and their therapeutic uses, particularly in the treatment of cancer. The present invention further includes methods and kits for the immunodetection and immunotherapy of cells for samples which express PCBP-1 antigens.
2. Background
One human carcinoma tumor antigen is PCBP-1 (poly(rC) binding protein-1). Pcbp-1 is an intronless human gene reported to have been generated by retrotransposition of a fully processed PCBP-2 mRNA. It is also reported to be located on chromosome 2 (70.17-70.17 Mb). The protein encoded by the Pcbp-1 gene is a reported multifunctional protein. PCBP-1, along with PCBP-2 and hnRNPK, are reported to form the major cellular poly(rC)-binding protein. Pcbp-1 has been sequenced. See UniProt Q15365, Q53SS8, Q14975; OMIM 601209; NCBI Gene 5093; NCBI RefSeq NP—006187; NCBI RefSeq NM—006196, NP—006187; NCBI UniGene 5093; and NCBI Accession AK130439, AAA91317. Homologues of Pcbp-1 are also reported, including, but not limited to, homologues of Pcbp-1 in the mouse (see NCBI UniGene 23983; UniProt P60335; and NCBI RefSeq NM—011865, NP—035995), dog, and rat.
PCBP-1 has also been reported to regulate transcription for a few individual promoters, to be important for the metabolism and gene expression of HIV-1 and poliovirus, and to stimulate IRES-mediated translation initiation in vitro and in vivo (Mitchell et al., 2003). It has also been reported to be modestly increased in the epidermis of elderly individuals (Gromov et al., Mol Cell Proteomics 2(2):70-84, 2003, herein incorporated by reference in its entirety).
Accordingly, there is a need for an antibody molecule to selectively detect diseases characterized by the expression or localization of Pcbp-1 gene products. There is also a need for an antibody molecule which has affinity for particular gene products of Pcbp-1.